Development of a Stacked Ensemble Model for Risk Stratification of Chronic Gvhd after Allogeneic HSCT: Trump Cohort Study

Background Effective risk stratification is vital for selecting donors and developing treatment strategies for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several pretransplant risk models have been proposed to predict post-transplant patient outcomes from pretransplant risk factors. However, it is still challenging to predict mid-to-long-term prognosis. To establish a novel and user-friendly tool for predicting chronic graft-versus-host disease (cGVHD), non-relapse mortality (NRM) and overall survival (OS), we used a Stacked Ensemble Model (SEM) designed to handle right-censored data and competing risk events (Iwasaki et al., 2021). Methods Using Japanese registry data, the Japanese Transplant Registry Unified Management Program, we analyzed 21,840 patients who underwent their first allo-HSCT between 2010 and 2018 for hematologic malignancies. Of these, 14,430 patients were alive without cGVHD and relapse on day 100 post-transplantation. Primary endpoint was cGVHD and secondary endpoints were NRM and OS. Data were randomly split into the training set (70% of the dataset) and the validation set (30%). We treated patient age and time from diagnosis to transplant as continuous variables and performance status, ABO type matching, sex matching, disease/status groups based on refined Disease Risk Index, Hematopoietic Cell Transplantation-specific Comorbidity Index, usage of total body irradiation, conditioning intensity, T cell depletion in vivo, human leukocyte antigen (HLA) locus matching, the number of HLA mismatching and CMV serostatus as categorical variables. To evaluate predictive accuracy at day 30, 60 and 100 posttransplant, we considered acute graft-versus-host disease (aGVHD) and its treatment, including grade 2 to 4 aGVHD occurrence, grade 3 to 4 aGVHD occurrence, stage of aGVHD before and after treatment, corticosteroid treatment, anti-thymocyte globulin treatment and treatment response of 1 st line therapy for aGVHD. Results The median age of the patients at transplantation was 51 years (inter quartile range (IQR): 39 - 60). The sources of stem cells were HLA-matched related bone marrow (BM) in 967 patients, HLA-matched related peripheral blood (PB) in 1,998 patients, haploidentical BM in 172 patients, haploidentical PB in 778 patients, unrelated BM in 5,539 patients, unrelated PB in 366 patients, and cord blood in 4,237 patients. Myeloablative conditioning was administered in 9,390 patients and reduced-intensity conditioning i